There is an increasing demand for the development of compounds having improved properties and which can be used against several different diseases, such as treatment of an infection or disease caused by a microorganism as well as for the stimulation or inhibition of the proliferation of eukaryotic cells as well as for other purposes.
One class of compounds, namely peptide derivatives based upon the inhibitory centre of human cystatin C, and the antibacterial properties thereof have been disclosed in Kasprzykowski et al., APMIS 2000, 108, 473-481.
WO 06/052201 discloses the use of peptide derivatives for the manufacture of a medicament for the treatment of microbial infections.
WO 07/129,952 discloses novel peptide derivatives and the use thereof as antimicrobial agent for treatment of wounds.
Hitherto no suggestions have been given for use of the mentioned peptide derivatives other than for antimicrobial and antibacterial purposes.
Osteoclasts constitute one type of eukaryotic cells. Bone resorption is a specific function of osteoclasts, which are multinucleated, specialized bone cells formed by the fusion of mononuclear progenitors originating from the hemopoietic compartment, more precisely from the granulocyte-macrophage colony-forming unit (GM-CFU). The osteoclast is the principal cell type for resorption of bone. Osteoclasts together with the bone-forming cells, the osteoblasts, dictate bone mass, bone shape and bone structure. Bone must undergo continuous resorption and renewal, a process collectively known as remodelling. During adult life bone remodelling is crucial to eliminate and replace structurally damaged or aged bone with structurally new healthy bone. To maintain the proper bone mass, resorption and formation are kept in perfect equilibrium. The balanced bone remodelling is disturbed in certain pathological conditions either to systemic excess or decrease of endocrine factors or the presence of local pathological conditions in the skeleton. In such diseases, the equilibrium between bone resorption and formation becomes altered, often in favour of resorption, resulting in a reduction in bone mass, deterioration of bone architecture, decreased resistance to stress, bone fragility, susceptibility to fractures or to disabilities in joints or teeth. Hence, increased activity and/or numbers of osteoclasts, relative to the activity and/or numbers of osteoblasts, may lead to a pathological loss of bone.
For conditions in which osteoclasts resorb bone at abnormally high levels as in osteoporosis, rheumatoid arthritis, periodontal disease, metastatic tumours, loss of joint prosthesis or tooth implant loss, the most reasonable therapeutic target would be the osteoclast. Decreasing the number of osteoclasts and/or the resorption activity of the osteoclasts, should restore the equilibrium between bone resorption and formation.